Impedance‐Based Multimodal Electrical‐Mechanical Intrinsic Flow Cytometry

Reflecting various physiological states and phenotypes of single cells, intrinsic biophysical characteristics (e.g., mechanical and electrical properties) are reliable and important, label-free biomarkers for characterizing single cells. However, single-modal mechanical or electrical properties alone are not specific enough to characterize single cells accurately, and it has been long and challenging to couple the conventionally image-based mechanical characterization and impedance-based electrical characterization. In this work, the spatial-temporal characteristics of impedance sensing signal are leveraged, and an impedance-based multimodal electrical-mechanical flow cytometry framework for on-the-fly high-dimensional intrinsic measurement is proposed, that is, Young's modulus E, fluidity β, radius r, cytoplasm conductivity σi , and specific membrane capacitance Csm , of single cells. With multimodal high-dimensional characterization, the electrical-mechanical flow cytometry can better reveal the difference in cell types, demonstrated by the experimental results with three types of cancer cells (HepG2, MCF-7, and MDA-MB-468) with 93.4% classification accuracy and pharmacological perturbations of the cytoskeleton (fixed and Cytochalasin B treated cells) with 95.1% classification accuracy. It is envisioned that multimodal electrical-mechanical flow cytometry provides a new perspective for accurate label-free single-cell intrinsic characterization.